Histamine regulates murine primary dendritic cell functions

Abstract

Objective and design: The modulation of antigen uptake and activation of dendritic cells (DCs) by histamine may function as a regulator of inflammation. Therefore, we sought to determine the impact of histamine on antigen uptake by and activation of murine DCs.

Material and methods: DCs from spleen and lung were either identified by flow cytometry or were immunomagnetically enriched. Cells were stimulated with histamine, and the regulation of MHC-II and co-stimulatory molecule expression (CD80, CD86, and ICOS-L) and antigen uptake were quantified by flow cytometry. Individual contributions of the histamine receptor subtypes were determined by using the antagonists mepyramine (histamine H₁-receptor: H₁R), famotidine (H₂R), and JNJ 7777120 (H₄R).

Results: Histamine accelerated the uptake of soluble antigen via the H₁R, H₂R, and H₄R in splenic DCs. Co-stimulatory molecule expression was enhanced already by enrichment procedures, thus, the analyses were performed in unseparated cell populations. Histamine enhanced the expression of CD86 and ICOS-L while expression of CD80 was unaffected. Antagonism at H₁R, H₂R, and H₄R and at H₁R and H₄R reduced the histamine-induced enhanced expression of CD86 and ICOS-L, respectively.

Conclusions: Histamine contributes to the regulation of the immunological synapse by stimulation of antigen uptake and activation of DCs via H₁R, H₂R, and H₄R.

Keywords:

• Histamine
• dendritic cells
• antigen uptake
• activation

Acknowledgements

The authors thank Renate Schottmann for excellent technical assistance and Drs. Schmiedl and Seifert for fruitful discussions.

Disclosure statement

The authors report that they have no conflicts of interest.

Funding

This work was supported by Deutsche Forschungsgemeinschaft SFB 587 (B17) and by the Hannover Medical School (Hannover Biomedical Research School program – StrucMed).